title: Relationship between CYP2D6 genotype and haloperidol pharmacokinetics and extrapyramidal symptoms in healthy volunteers.
abstract: OBJECTIVE
  This study aimed to elucidate the relationship between CYP2D6 genotype and haloperidol pharmacokinetics and induced extrapyramidal symptoms (EPSs).
  
  
  METHODS
  Twenty five healthy subjects were included in this randomized, placebo-controlled, single-dose (5 mg) crossover and double-blind clinical trial, selected according to their CYP2D6 genotype and classified as poor metabolizers (n = 8), extensive metabolizers (n = 10) and ultrarapid metabolizers (n = 7).
  
  
  CONCLUSIONS
  We confirm that CYP2D6 genotype partially determines haloperidol metabolism and the rate of EPSs measured as wakefulness activity by actigraphy. The best predictor of wakefulness activity was the model including haloperidol area under the plasma concentration-time curve, sex and tranquilization, which explained 48.3% of the total variance. However, other markers need to be identified in order to explain the observed variability of haloperidol response and to develop pharmacogenetic predictors of haloperidol-induced EPSs.
authors.affiliation: Department of Anatomic Pathology, Pharmacology & Microbiology, School of Medicine, University of Barcelona, IDIBAPS, Casanova 143, E-08036 Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Gassó
authors.forename: Katerina
authors.initials: K
authors.lastname: Papagianni
authors.forename: Sergi
authors.initials: S
authors.lastname: Mas
authors.forename: Ramón Fernández
authors.initials: RF
authors.lastname: de Bobadilla
authors.forename: Joan Albert
authors.initials: JA
authors.lastname: Arnaiz
authors.forename: Miquel
authors.initials: M
authors.lastname: Bernardo
authors.forename: Amalia
authors.initials: A
authors.lastname: Lafuente
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001480:Basal Ganglia Diseases / Q000139:chemically induced*; D018592:Cross-Over Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006220:Haloperidol / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult
chemical_list: D019389:Cytochrome P-450 CYP2D6; D006220:Haloperidol